title: Aneuploidy underlies a multicellular phenotypic switch.
abstract: Although microorganisms are traditionally used to investigate unicellular processes, the yeast Saccharomyces cerevisiae has the ability to form colonies with highly complex, multicellular structures. Colonies with the "fluffy" morphology have properties reminiscent of bacterial biofilms and are easily distinguished from the "smooth" colonies typically formed by laboratory strains. We have identified strains that are able to reversibly toggle between the fluffy and smooth colony-forming states. Using a combination of flow cytometry and high-throughput restriction-site associated DNA tag sequencing, we show that this switch is correlated with a change in chromosomal copy number. Furthermore, the gain of a single chromosome is sufficient to switch a strain from the fluffy to the smooth state, and its subsequent loss to revert the strain back to the fluffy state. Because copy number imbalance of six of the 16 S. cerevisiae chromosomes and even a single gene can modulate the switch, our results support the hypothesis that the state switch is produced by dosage-sensitive genes, rather than a general response to altered DNA content. These findings add a complex, multicellular phenotype to the list of molecular and cellular traits known to be altered by aneuploidy and suggest that chromosome missegregation can provide a quick, heritable, and reversible mechanism by which organisms can toggle between phenotypes.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Tan
authors.forename: Michelle
authors.initials: M
authors.lastname: Hays
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Cromie
authors.forename: Eric W
authors.initials: EW
authors.lastname: Jeffery
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Scott
authors.forename: Vida
authors.initials: V
authors.lastname: Ahyong
authors.forename: Amy
authors.initials: A
authors.lastname: Sirr
authors.forename: Alexander
authors.initials: A
authors.lastname: Skupin
authors.forename: Aimée M
authors.initials: AM
authors.lastname: Dudley
mesh_terms: D000782:Aneuploidy; D015825:Chromosomes, Fungal; D018628:Gene Dosage; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*
keywords: bet-hedging; colony morphology; copy number variation; phenotypic switching